chr16-23388920-T-A

Position:

• chr16-23388920-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_153603.4(COG7):​c.2313A>T​(p.Ter771CysextTer62) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: COG7 NM_153603.4 stop_lost
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.50

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_153603.4 Downstream stopcodon found after 2 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG7	NM_153603.4	c.2313A>T	p.Ter771CysextTer62	stop_lost	17/17	ENST00000307149.10
COG7	XM_017023870.2	c.2118A>T	p.Ter706CysextTer62	stop_lost	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG7	ENST00000307149.10	c.2313A>T	p.Ter771CysextTer62	stop_lost	17/17	1	NM_153603.4	P1
COG7	ENST00000566364.1	n.660A>T		non_coding_transcript_exon_variant	3/3	2
COG7	ENST00000561854.1	c.*405A>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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The COG7 p.(*771Cysext*62) variant is stoploss variant which causes an elongated of the protein's amino acid sequence adding 62 codons onto the sequence. This c.2313A>T variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, Cosmic, MutDB or LOVD 3.0 databases. The variant was not identified in the following control databases: the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The impact of this stoploss alteration on COG7 protein function is not known, however this variant was predicted to be a polymorphism by MutationTaster. This information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	16
DANN	Benign	0.66
Eigen	Pathogenic	0.81
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
MutationTaster	Benign	1.0	N
Vest4		0.0030
GERP RS		4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1963139535; hg19: chr16-23400241;